Thesis
Non-destructive estimation of particle size in granular compacts by terahertz scattering
- Creator
- Rights statement
- Awarding institution
- University of Strathclyde
- Date of award
- 2024
- Thesis identifier
- T16919
- Person Identifier (Local)
- 201980029
- Qualification Level
- Qualification Name
- Department, School or Faculty
- Abstract
- Particle size measurements in granular compacts are crucial for various industries, particularly pharmaceuticals, to ensure product quality and efficiency. In the pharmaceutical industry, variations in particle size of either active pharmaceutical ingredients (APIs) or excipients occur throughout the manufacturing process. Particle size variation in pharmaceutical products has been extensively investigated and is linked to altered dissolution performance, thus impacting the efficacy and quality of the final product. However, current methods for particle size monitoring are predominantly offline and destructive, bearing various inherent limitations. This necessitates the need for innovative techniques. An ideal solution would encompass various characteristics, such as allowing for non-destructive in-situ monitoring during the manufacturing process. To this end, the application of terahertz time-domain spectroscopy (THz-TDS) as a technique for quantifying particle or domain size in granular compacts is considered. Samples were developed comprising a mixture of polymer powder and borosilicate microspheres, allowing for the isolation of particle size and concentration in compacts. Multiple polymer materials were compacted and analysed at various pressures to minimise sample porosity while ensuring sufficient compact strength for further handling. It was determined that polytetrafluoroethylene (PTFE) was the preferred matrix material with acceptable tensile strength and exhibiting minimal porosity if compacted at 392 MPa. Finally, ten borosilicate microsphere samples were fabricated at six concentration levels and five particle sizes to isolate the effect of particle size and concentration on THz scattering. Employing THz-TDS, each compact and optical grade borosilicate glass windows were analysed at low frequencies (<1.2 THz) before extraction of the scattering contributions to the loss coefficient. It was observed that the scattering increased linearly at low concentrations before the onset of saturation and subsequently decreased at higher concentrations. Additionally, the typical approach to scattering analysis via power law fitting was investigated, and the dependence of the fitting parameters was determined, with the exponent being solely dependent on concentration. The pre-exponent was dependent on particle size and concentration, leading to the potential for particle size estimation with simple linear fitting. Furthermore, complex pharmaceutical compacts fabricated at various compaction pressures and API particle sizes are analysed using THz-TDS. The extracted loss coefficient suggested that API agglomeration occurred in smaller particle-size batches, increasing the loss coefficient at THz frequencies. Subsequent near-infrared chemical imaging confirmed the presence of API agglomeration. The use of power law fitting allowed for the development of a linear model (𝑅𝑅2= 0.91) for the non-destructive estimation of agglomerate size. This work highlights the applicability of THz-TDS for the estimation of particle size changes in granular compacts with the aid of a linear model. The thesis culminates with an unexpected discovery upon extending the scattering analysis to higher frequencies. The emergence of spurious peaks was observed, attributed to multiple paths of photon propagation through a mixture. This finding raises concerns for confidence in THz-TDS measurements at higher frequencies (>2 THz); therefore, further work is recommended. However, it should be noted that the analysis in chapters 3-5 was conducted at lower frequencies where this effect is negligible. This thesis underscores the applicability of THz-TDS for estimating particle size changes in granular compacts while providing crucial insights into other material characteristics, such as sample porosity. Additionally, it advances our current understanding of scattering in the terahertz region, specifically in mixed materials. Finally, a concerning finding is highlighted that could significantly impact the reproducibility and accuracy of THz-TDS analysis of granular compacts at high frequencies.
- Advisor / supervisor
- Markl, Daniel
- Naftaly, Mira
- Nordon, Alison
- Resource Type
- Note
- This thesis was previously held under moratorium from 10th May 2024 until 10th May 2026.
- DOI
Relations
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